The secretory cells lining the oviductal lumen in human and nonhuman primates synthesize and secrete an estrogen-dependent oviduct-specific 120 kD glycoprotein (OGP). OGP is the major nonserum protein present in the oviductal lumen at the time of ovulation, fertilization and early embryonic development. OGP cDNAs from various species are highly homologous and the message levels in the primate are increased by estradiol and decreased by progesterone. OGP associates with the zona pellucida of oviductal eggs and embryos and increases the rate of sperm penetration of the zona pellucida. Passive immunization using an antibody against OGP in the hamster significantly decreased fertilization efficiency. The hypothesis that we propose to test is that OGP, by specifically binding to the zona pellucida modifies the zona pellucida sperm receptor and/or other zona pellucida proteins, thus enhancing sperm binding and promoting the penetration process. This will be accomplished using two in vitro systems, namely the human hemizona assay and a rhesus IVF system. Specific parameters to be monitored include sperm bound/hemizona, sperm penetration rates, fertilization rates and binding of OGP to specific labeled zona proteins. The function of OGP will be further tested in vivo in the hamster using active immunology techniques. We also propose to generate human recombinant core and glycosylated molecules and test their biological properties in the human hemizona assay. We believe OGP plays a key physiological role(s) in prefertilization (sperm activation, sperm binding to zona, zona penetration) reproductive events. The ability to demonstrate a clear role in prefertilization events has important implications in at least two areas of human fertility control, namely, a biologically active recombinant OGP molecule could potentially become an important additive to current human IVF media, and OGP could be a new prefertilization immunocontraceptive target. Additionally, the proposed studies will provide new insight into primate oviductal physiology and the fertilization process.